ASCO24: Pfizer's Lorbrena achieves new lung cancer survival milestone

Pfizer's Lorbrena (lorlatinib) has redefined expectations for long-term outcomes in ALK-positive non-small-cell lung cancer (NSCLC), showcasing groundbreaking five-year progression-free survival (PFS) statistics at the American Society of Clinical Oncology (ASCO) annual meeting. This update from the Phase III CROWN trial is expected to bolster the adoption of Lorbrena as a first-line treatment for ALK-positive advanced NSCLC, a space currently dominated by Roche’s Alecensa (alectinib).

CROWN Trial Findings

The Phase III CROWN study included approximately 300 treatment-naïve ALK-positive patients who were randomized to receive either Lorbrena or Pfizer's Xalkori (crizotinib). Initially approved through an accelerated pathway in 2018, Lorbrena received full approval in the U.S. as a front-line treatment in 2021, based on data showing a 72% reduction in the risk of progression or death compared to Xalkori over an 18-month period.

Remarkable Progression-Free Survival

Principal investigator Benjamin Solomon highlighted the significance of the new findings, noting that the benefit seen corresponds to the longest PFS ever reported in ALK-positive NSCLC and possibly any targeted lung cancer therapy to date. After a median follow-up of 60.2 months, Lorbrena was associated with an 81% reduced risk of progression or death. While median PFS for the Xalkori arm was 9.1 months, it has yet to be reached in the Lorbrena arm. At the five-year mark, PFS rates for Lorbrena and Xalkori were 60% and 8%, respectively. Overall survival data is still being collected as the required number of events has not been reached for a full analysis.

Efficacy Against Brain Metastases

One of the standout attributes of Lorbrena is its efficacy against brain metastases, which has been found to be superior to Alecensa and Takeda’s Alunbrig (brigatinib). In patients with existing brain metastases, who made up about a quarter of the CROWN study's population, the probability of being free from intracranial progression at five years was 83% with Lorbrena, compared to rapid progression with Xalkori. For patients without brain metastases, the probability rose to 96%. Lorbrena’s PFS benefit was superior to Xalkori regardless of brain metastases, with PFS rates of 53% and 63%, respectively, among Lorbrena-treated patients at the five-year mark. Solomon remarked that these results illustrate Lorbrena's ability to prevent and delay the progression of both existing and new brain metastases.

Choosing the Right Treatment

A key opinion leader (KOL) noted that the choice between treatments often hinges on intracranial benefits and side-effect profiles. Alecensa is associated with mild gastrointestinal symptoms and swelling, whereas Lorbrena raises concerns about hypercholesterolemia and neurotoxicity, sometimes necessitating dose adjustments. Despite these side effects, both drugs offer significant benefits to patients, with Lorbrena being particularly advantageous in managing CNS disease.

Safety Profile

The latest CROWN update did not reveal any new safety signals for Lorbrena, adding to its appeal as a first-line treatment option in this challenging clinical setting.

In conclusion, Pfizer's Lorbrena has set a new standard in the treatment of ALK-positive NSCLC, offering unprecedented long-term PFS and significant advantages in managing brain metastases, positioning it as a strong competitor in the field.

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